Despite years of intensive investigation, the prognosis for most patients with anaplastic central nervous system (CNS) tumors remains poor. Median survival for adults with the most common form of CNS tumor, the glioblastoma multiforme, is 8-12 months. The outlook is somewhat better for less common tumors such as anaplastic astrocytoma and medulloblastoma, but most primary anaplastic CNS tumors are highly resistant to currently available therapy.
Only radiotherapy has been shown to prolong survival in patients with anaplastic gliomas. Following conventional therapy with surgery and external beam radiotherapy, malignant gliomas tend to recur at or near the original tumor site. Temporarily implanted radioactive iodine sources (interstitial brachytherapy) have recently been used to deliver high dose focal radiotherapy to locally recurrent malignant gliomas.
Radiotherapy is also utilized in the treatment of CNS melanoma. Response rates vary from 37% to 100%. The reported mean duration of response to palliative radiotherapy in CNS melanoma varies from 2 to 5 months, and mean survival following irradiation ranges from 2 to 7.6 months (average 3.8 months). No single treatment regimen has been shown to be superior in improving response rate and survival time. See Mastrangelo et al., In Cancer: Principles and Practices of Oncology, pp. 1403-1404 (DeVita, Hellman & Rosenberg Eds. 1985). Nevertheless, satisfactory treatments are not yet available for CNS cancers, and there is a continued need for new treatments for these diseases.
The possibility of using therapeutic antibodies to treat CNS neoplasms is beginning to be investigated. R. Moseley et al., Br. J. Cancer 62, 637 (1990) describe the intrathecal administration of .sup.131 I radiolabelled monoclonal antibody for the treatment of neoplastic meningitis.
The use of intact ME1-14 to treat three patients with CNS melanoma is described in L. Lashford et al., Cancer 61, 857 (1988), and Moseley et al., Br. J. Cancer, 62, 637 (1990).
The F(Ab').sub.2 fragment of Me1-14 also localized specifically in paired-label studies to human glioma xenografts in athymic mice and has been administered and shown to localize specifically and similarly in human gliomas in the brain of patients. See M. Zalutsky et al., Cancer Res., 50, 4105, (1990); Behnke et al., Brit. J. Neurosurg. 2,193, (1988); Behnke et al., In Brain Oncology--Biology, Diagnosis, and Therapy, pp. 125-128 (Chatel et al., Eds. 1987).
Systemically administered .sup.131 I-labeled Me1-14 F(Ab').sub.2 to mice bearing intracerebral human D-54 MG xenografts is described in Colapinto et al., Cancer Res., 50, 1822 (1990).